Real-life use of remdesivir-containing regimens in COVID-19: a retrospective case-control study.

Background: Remdesivir (REM) has shown potent antiviral activity in vitro and efficacy in animal models of COVID-19; nevertheless, clinical trials and real-life reports have shown conflicting data on its effectiveness. Aims of the study were to evaluate the impact of remdesivir on I) Intensive Care Unit (ICU) admission, II) need for orotracheal intubation (OTI) and III) in-hospital mortality. Furthermore, we estimated the kinetics of laboratory parameters and assessed the risk factors for in-hospital mortality in the remdesivir population. Methods: We conducted a retrospective, single-center, case-control (1:1) study including hospitalized patients with confirmed SARS-CoV-2 infection. Cases were patients treated with remdesivir for 5 days, controls were patients not receiving remdesivir. Results: A total of 192 patients (96 cases and 96 controls) were included in the study. Patients receiving remdesivir had a lower rate of ICU admission and need for OTI than controls, whereas no difference between cases and controls were observed as for mortality rate. However, at multivariable analysis remdesivir was not associated with ICU admission neither with OTI. Instead, presence of haematological malignancies, lower duration of symptoms, higher severity of infection and low lymphocytes count at admission were independently associated with in-hospital mortality. In patients treated with remdesivir a low albumin value and duration of lymphopenia were significantly associated with mortality. Conclusions: Our real-life study showed that therapy with remdesivir did not have impact on either ICU admission, need for OTI or in-hospital mortality.

An outbreak sustained by ST15 Klebsiella pneumoniae carrying 16S rRNA methyltransferases and blaNDM: evaluation of the global dissemination of these resistance determinants.

The spread of extremely-drug-resistant Klebsiella pneumoniae has become a major health threat worldwide. This is largely mediated by certain lineages, recognized as high-risk clones dispersed throughout the world. Analysis of an outbreak of nine ST15, NDM-1 metallo-ß-lactamase-producing K. pneumoniae was performed. An IncC plasmid carrying the blaNDM-1 gene also carried the rare rmtC gene, encoding for 16S rRNA methyltransferases (16RMTases), conferring resistance to all aminoglycosides. The global spread of New Delhi metallo (NDM) variants and their association with the 16RMTases among K. pneumoniae complete genomes available in GenBank was studied, and a complete overview of the association of 16RMTases and NDM in K. pneumoniae genomics was produced. NDM is often associated with16RMTases, and both are spreading in K. pneumoniae, conferring resistance to all beta-lactams and aminoglycosides. This analysis suggests that aminoglycosides have a limited future as a second-line treatment against NDM-producing K. pneumoniae.

Role of Serum E-Selectin as a Biomarker of Infection Severity in Coronavirus Disease 2019.

INTRODUCTION: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis. METHODS: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed. RESULTS: One hundred patients were included, with a median age (IQR) of 65 years (58-78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1-35). sE-selectin values did not differ between deceased and survivors (p = 0.06) and among patients with or without a thrombotic event (p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO2/FiO2 < 200 and PaO2/FiO2 200-300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 (p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 (p = 0.004)). CONCLUSIONS: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity.

Persistent Systemic Microbial Translocation and Intestinal Damage During Coronavirus Disease-19.

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.

Ozone as adjuvant support in the treatment of COVID-19: A preliminary report of probiozovid trial.

The evaluation of new therapeutic resources against coronavirus disease 2019 (COVID-19) represents a priority in clinical research considering the minimal options currently available. To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. PROBIOZOVID is an ongoing, interventional, randomized, prospective, and double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone-autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-ozone administration for 7 days. All patients were treated with ad interim best available therapy. The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, hematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8.3% for ozone group and 10% for controls. Ozone therapy did not significantly influence inflammation markers, hematology profile, and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although did not reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity.

Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19.

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.